Acute pancreatitis is a frequently lethal inflammatory disease of the pancreas which is thought to involve autodigestion of the pancreas by its own digestive enzymes. The proposed studies will evaluate pancreatic acinar cell changes which accompany the development of this disease or exposure of the pancreas to agents believed to cause acute pancreatitis. These studies will utilize the mouse pancreas as the experimental system. Pancreatitis will be elicited in-vivo using an ethionine-enriched, choline-deficient diet, and the pancreas subsequently studied in-vitro in one series of experiments. In these experiments, acute in-vivo pancreatitis will be elicited by several means including dietary manipulation, hypersensitivity reaction, and duodenal-pancreatic duct reflux. In other studies, the in-vitro pancreas will be exposed to supposedly harmful agents such as ethanol, lecithin, and certain drugs. The proposed studies will search for changes in the normal pattern of digestive enzyme synthesis, intracellular transport and secretion which accompany acute pancreatitis. The possible intracellular release of digestive enzymes and changes in membrane integrity with this disease will be studied. Other studies will characterize the pancreatic juice during acute pancreatitis and search for the presence of activated proteolytic enzymes as well as changes in enzyme inhibitors. It is believed that these studies will unravel some of the mysteries which surround acute pancreatitis and provide clues as to how this disease can be prevented and/or more effectively treated.